A terriying family inheritAnce
The mystery of Fatal familial insomnia
begin the investigation
Welcome Medical Investigators
Your task is to solve the medical mystery of Fatal Familial Insomnia.To complete the investigation, you must explore each section of the house and gather clues about the disorder.How to Play:1. Select an area of the house to investigate.2. Review the information and examine the evidence.3. Answer the question associated with each section.4. Correct answers will unlock the next part of the investigation.Investigation Areas- Pedigree Analysis and Genetic Inheritance- Sleep and Circadian Rhythm- Epidemiology and History- Symptoms and Treatment- Diagnosis and TestingAfter you have explored all areas and collected the clues, you will review the case files and determine the final diagnosis.
Case Briefing
Fatal familial insomnia (FFI) is a rare genetic condition that affects your brain and central nervous system. It causes you to have trouble sleeping (insomnia), memory loss (dementia) and muscle twitching. FFI is degenerative, which means symptoms get more severe over time. Symptoms of the condition are life-threatening and there’s no cure. FFI affects people who inherit the mutation in the PRNP gene from one of their biological parents. There’s usually a history of the condition affecting the family since only one copy of the mutated gene is enough to cause symptoms (autosomal dominant). In extremely rare cases, FFI can occur in people who don’t have a history of the condition in their family. In these cases, the condition happens with a new genetic mutation (de novo).
Your task is to analyze the evidence and determine how this disorder affects the brain.
Investigation Briefing: Fatal Familial Insomnia
Diagnosis & Tests
Explore the house
Symptoms & Treatment
Inventory
Pedigree Analysis and Genetic Inheritance
Epidemiology and History
Sleep & Circadium System
01
Symptoms
Symptoms of fatal familial insomnia include:
- Difficulty sleeping that gets worse over time (progressive insomnia).
- Nervous system overactivity including high blood pressure, a faster-than-normal heart rate and anxiety.
- Involuntary muscle twitching or jerking (myoclonus).
Symptoms of FFI begin between the ages of 20 and 70. The average age of symptom onset is 40.
Early symptoms of FFI can look similar to those of dementia and Alzheimer’s disease
02
The investigation deepens. Family member reports describe worsening insomnia, confusion, and neurological decline. Doctors attempted several treatments, but the disease continued to progress. To move forward, investigators must identify the most common symptom of Fatal Familial Insomnia.
How is fatal familial insomnia diagnosed?
A healthcare provider diagnoses fatal familial insomnia (FFI) by reviewing symptoms and offering tests to confirm the diagnosis. Tests could include:
- Polysomnography: Sleep test to detect sleep pattern abnormalities.
- Electroencephalogram (EEG): Test to measure electrical activity in your brain.
- Cerebrospinal Fluid (CSF) analysis: This test examines cerebrospinal fluid (fluid in your brain and spinal cord) to identify conditions that affect the brain and spinal cord.
- Genetic testing to identify the gene responsible for symptoms.
- Imaging tests: MRI, CT scan or PET scan.
- Labs like a complete blood count (CBC), liver function test and blood cultures.
224
02
Medical records are scattered across the table. Lab reports, brain scans, and sleep studies reveal clues about the mysterious disorder affecting this family. Investigators must determine how doctors confirm the presence of Fatal Familial Insomnia.
Pedigree Analysis and Genetic Inheritance
Scientists use pedigree analysis to study how genetic disorders are passed through families. A pedigree chart is a diagram that tracks the inheritance of traits across multiple generations. Fatal Familial Insomnia follows an autosomal dominant inheritance pattern. Autosomal means the gene involved is located on one of the numbered chromosomes. Dominant means that a child only needs to inherit one copy of the mutated gene, from either biological parent, to be affected by the disease. If one parent carries the PRNP gene mutation, each child has approximately a 50% chance of inheriting the mutation. Pedigree studies were critical in identifying Fatal Familial Insomnia because researchers observed the disorder appearing repeatedly across generations within the same families. These patterns helped scientists trace the disease to the PRNP gene mutation responsible for abnormal prion proteins.
224
Pedigree Chart
224
01
Fatal Familial Insomnia is a rare autosomal dominant genetic disorder, meaning the mutation can be inherited when only one copy of the gene is altered. Researchers discovered that the disorder is caused by a mutation in a gene responsible for producing prion proteins. When this protein misfolds, it leads to progressive neurodegeneration affecting sleep regulation. To unlock the next room, identify the gene responsible for this mutation.
Sleep and Circadian Rhythm in Fatal Familial Insomnia
Sleep is regulated by a network of brain structures that coordinate circadian rhythm and sleep–wake cycles. The suprachiasmatic nucleus (SCN) in the hypothalamus acts as the body’s master circadian clock, receiving light information from the retina and synchronizing the 24-hour sleep–wake cycle.
In Fatal Familial Insomnia, abnormal prion proteins accumulate primarily in the thalamus, a key relay structure involved in sleep regulation. The thalamus normally helps coordinate communication between the reticular activating system (RAS) in the brainstem and the cerebral cortex, allowing the brain to transition between wakefulness and sleep.
When the thalamus is damaged, this communication is disrupted, preventing the brain from generating normal sleep rhythms and restorative sleep stages.
Investigating the Brain's Clock
Sleep is controlled by an internal biological timer known as the circadian rhythm. Deep within the brain, a small cluster of neurons regulates this 24-hour cycle, helping the body know when to wake and when to rest. In Fatal Familial Insomnia, this delicate system is disrupted. To uncover the next clue, identify the structure that serves as the brain’s master circadian clock.
03
Epidemiology and History of Fatal Familial Insomnia
Fatal Familial Insomnia (FFI) is a rare genetic prion disease first described in the 1980s by Italian neurologist Elio Lugaresi and his colleagues at the University of Bologna. The disorder was identified after researchers investigated several families in Italy experiencing a mysterious illness characterized by severe insomnia and neurological decline. The disease is called Fatal Familial Insomnia because it is fatal, occurs within families, and primarily affects the brain’s ability to regulate sleep. Scientists later discovered that the disorder is caused by a mutation in the PRNP gene, which leads to misfolded prion proteins that damage the brain, particularly the thalamus. From an epidemiological perspective, FFI is extraordinarily rare. Researchers estimate that fewer than 70 families worldwide carry the mutation responsible for the disorder. Most documented cases have been reported in Europe, especially Italy and other parts of the Mediterranean region, although additional families have been identified in North America, Asia, and Australia.
01
01
A set of old research notes lies on the desk. The documents describe a mysterious illness affecting several families, where patients gradually lost the ability to sleep and experienced severe neurological decline. In the 1980s, a neurologist studying these families began documenting the disorder, helping researchers understand that the illness was a rare inherited prion disease now known as Fatal Familial Insomnia. To unlock the next room, identify the neurologist who first described this disorder.
Case Closed:
Through this investigation, we uncovered the key clues behind Fatal Familial Insomnia:
- A mutation in the PRNP gene
- Misfolded prion proteins
- Degeneration of the thalamus
- Disruption of the brain’s ability to generate sleep
Although rare, this disorder highlights how genetics and brain systems interact to regulate one of the most essential human functions: sleep.
Are you sure you want to exit?
You will lose all progress so far...
Back
Exit
Someone is there!
Inventory
Inventory
Inventory
Inventory
Inventory
♪♬ø
Inventory
Inventory
The mystery of Fatal familial insomnia
Kelley B
Created on April 1, 2026
Start designing with a free template
Discover more than 1500 professional designs like these:
View
Vibrant Breakout
View
Reboot Protocol
View
Science Breakout
View
Mystery Breakout
View
Musical Room Escape
View
Submarine Escape Game
View
Earth Day Escape Room
Explore all templates
Transcript
A terriying family inheritAnce
The mystery of Fatal familial insomnia
begin the investigation
Welcome Medical Investigators
Your task is to solve the medical mystery of Fatal Familial Insomnia.To complete the investigation, you must explore each section of the house and gather clues about the disorder.How to Play:1. Select an area of the house to investigate.2. Review the information and examine the evidence.3. Answer the question associated with each section.4. Correct answers will unlock the next part of the investigation.Investigation Areas- Pedigree Analysis and Genetic Inheritance- Sleep and Circadian Rhythm- Epidemiology and History- Symptoms and Treatment- Diagnosis and TestingAfter you have explored all areas and collected the clues, you will review the case files and determine the final diagnosis.
Case Briefing
Fatal familial insomnia (FFI) is a rare genetic condition that affects your brain and central nervous system. It causes you to have trouble sleeping (insomnia), memory loss (dementia) and muscle twitching. FFI is degenerative, which means symptoms get more severe over time. Symptoms of the condition are life-threatening and there’s no cure. FFI affects people who inherit the mutation in the PRNP gene from one of their biological parents. There’s usually a history of the condition affecting the family since only one copy of the mutated gene is enough to cause symptoms (autosomal dominant). In extremely rare cases, FFI can occur in people who don’t have a history of the condition in their family. In these cases, the condition happens with a new genetic mutation (de novo).
Your task is to analyze the evidence and determine how this disorder affects the brain.
Investigation Briefing: Fatal Familial Insomnia
Diagnosis & Tests
Explore the house
Symptoms & Treatment
Inventory
Pedigree Analysis and Genetic Inheritance
Epidemiology and History
Sleep & Circadium System
01
Symptoms
Symptoms of fatal familial insomnia include:
Symptoms of FFI begin between the ages of 20 and 70. The average age of symptom onset is 40. Early symptoms of FFI can look similar to those of dementia and Alzheimer’s disease
02
The investigation deepens. Family member reports describe worsening insomnia, confusion, and neurological decline. Doctors attempted several treatments, but the disease continued to progress. To move forward, investigators must identify the most common symptom of Fatal Familial Insomnia.
How is fatal familial insomnia diagnosed?
A healthcare provider diagnoses fatal familial insomnia (FFI) by reviewing symptoms and offering tests to confirm the diagnosis. Tests could include:
224
02
Medical records are scattered across the table. Lab reports, brain scans, and sleep studies reveal clues about the mysterious disorder affecting this family. Investigators must determine how doctors confirm the presence of Fatal Familial Insomnia.
Pedigree Analysis and Genetic Inheritance
Scientists use pedigree analysis to study how genetic disorders are passed through families. A pedigree chart is a diagram that tracks the inheritance of traits across multiple generations. Fatal Familial Insomnia follows an autosomal dominant inheritance pattern. Autosomal means the gene involved is located on one of the numbered chromosomes. Dominant means that a child only needs to inherit one copy of the mutated gene, from either biological parent, to be affected by the disease. If one parent carries the PRNP gene mutation, each child has approximately a 50% chance of inheriting the mutation. Pedigree studies were critical in identifying Fatal Familial Insomnia because researchers observed the disorder appearing repeatedly across generations within the same families. These patterns helped scientists trace the disease to the PRNP gene mutation responsible for abnormal prion proteins.
224
Pedigree Chart
224
01
Fatal Familial Insomnia is a rare autosomal dominant genetic disorder, meaning the mutation can be inherited when only one copy of the gene is altered. Researchers discovered that the disorder is caused by a mutation in a gene responsible for producing prion proteins. When this protein misfolds, it leads to progressive neurodegeneration affecting sleep regulation. To unlock the next room, identify the gene responsible for this mutation.
Sleep and Circadian Rhythm in Fatal Familial Insomnia
Sleep is regulated by a network of brain structures that coordinate circadian rhythm and sleep–wake cycles. The suprachiasmatic nucleus (SCN) in the hypothalamus acts as the body’s master circadian clock, receiving light information from the retina and synchronizing the 24-hour sleep–wake cycle. In Fatal Familial Insomnia, abnormal prion proteins accumulate primarily in the thalamus, a key relay structure involved in sleep regulation. The thalamus normally helps coordinate communication between the reticular activating system (RAS) in the brainstem and the cerebral cortex, allowing the brain to transition between wakefulness and sleep. When the thalamus is damaged, this communication is disrupted, preventing the brain from generating normal sleep rhythms and restorative sleep stages.
Investigating the Brain's Clock
Sleep is controlled by an internal biological timer known as the circadian rhythm. Deep within the brain, a small cluster of neurons regulates this 24-hour cycle, helping the body know when to wake and when to rest. In Fatal Familial Insomnia, this delicate system is disrupted. To uncover the next clue, identify the structure that serves as the brain’s master circadian clock.
03
Epidemiology and History of Fatal Familial Insomnia
Fatal Familial Insomnia (FFI) is a rare genetic prion disease first described in the 1980s by Italian neurologist Elio Lugaresi and his colleagues at the University of Bologna. The disorder was identified after researchers investigated several families in Italy experiencing a mysterious illness characterized by severe insomnia and neurological decline. The disease is called Fatal Familial Insomnia because it is fatal, occurs within families, and primarily affects the brain’s ability to regulate sleep. Scientists later discovered that the disorder is caused by a mutation in the PRNP gene, which leads to misfolded prion proteins that damage the brain, particularly the thalamus. From an epidemiological perspective, FFI is extraordinarily rare. Researchers estimate that fewer than 70 families worldwide carry the mutation responsible for the disorder. Most documented cases have been reported in Europe, especially Italy and other parts of the Mediterranean region, although additional families have been identified in North America, Asia, and Australia.
01
01
A set of old research notes lies on the desk. The documents describe a mysterious illness affecting several families, where patients gradually lost the ability to sleep and experienced severe neurological decline. In the 1980s, a neurologist studying these families began documenting the disorder, helping researchers understand that the illness was a rare inherited prion disease now known as Fatal Familial Insomnia. To unlock the next room, identify the neurologist who first described this disorder.
Case Closed:
Through this investigation, we uncovered the key clues behind Fatal Familial Insomnia:
Although rare, this disorder highlights how genetics and brain systems interact to regulate one of the most essential human functions: sleep.
Are you sure you want to exit?
You will lose all progress so far...
Back
Exit
Someone is there!
Inventory
Inventory
Inventory
Inventory
Inventory
♪♬ø
Inventory
Inventory